Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders

Abstract

Although nonmyeloablative conditioning regimen transplantations (NMTs) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, graft-versushost disease (GVHD) remains a significant cause of morbidity and mortality. In vivo T-cell depletion, using alemtuzumab, has been shown to reduce the incidence of GVHD. However, this type of maneuver, although reducing GVHD, may have an adverse impact on disease response, because NMTs exhibit their antitumor activity by relying on a graft-versus-malignancy effect. To explore the efficacy of alemtuzumab compared with methotrexate (MTX) for GVHD prophylaxis, we have compared the results in 129 recipients of a sibling NMT enrolled in 2 prospective studies for chronic lymphoproliferative disorders. Both NMTs were based on the same combination of fludarabine and melphalan, but the United Kingdom regimen (group A) used cyclosporin A plus alemtuzumab, whereas the Spanish regimen (group B) used cyclosporin A plus MTX for GVHD prophylaxis. Patients receiving alemtuzumab had a higher incidence of cytomegalovirus (CMV) reactivation (85% versus 24%, P < .001) and a significantly lower incidence of acute GVHD (21.7% versus 45.1%, P ‫؍‬ .006) and chronic GVHD (5% versus 66.7%, P < .001). Twenty-one percent of patients in group A and 67.5% in group B had complete or partial responses 3 months after transplantation (P < .001). Eighteen patients in group A received donor lymphocyte infusions (DLIs) to achieve disease control.At last follow-up there was no difference in disease status between the groups with 71% versus 67.5% (P ‫؍‬ .43) of patients showing complete or partial responses in groups A and B, respectively. No significant differences were observed in event-free or overall survival between the 2 groups. In conclusion, alemtuzumab significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving alemtuzumab often required DLIs to achieve similar tumor control but the incidence of GVHD was not significantly increased after DLI. (Blood. 2002;100: 3121-3127)

Reduced-intensity conditioning prior to allogeneic transplantation of hematopoietic stem cells: the need for T cells early after transplantation to induce a graft-versus-lymphoma effect

“…Our observations are in line with those reported by Perez-Simon et al 24 , who compared the results of RIC with or without alemtuzumab in patients with lymphoma and related diseases transplanted in the UK and Spain. Alemtuzumab as a very effective means of in vivo T-cell depletion led to significantly less GVHD and TRM, but a GVL effect became obvious after DLI only in the majority of patients.…”

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

“…9 In consequence, GVHD (acute and/ or chronic) occurs spontaneously in most patients. 7,9,17 We and others have observed a strong association between GVHD and decreased risk of disease progression in both myeloid and lymphoid malignancies. 9,[18][19][20][21] The occurrence of moderate to severe GVHD, however, also increases the risk of developing life-threatening infections.…”

Alemtuzumab markedly reduces chronic GVHD without affecting overall survival in reduced-intensity conditioning sibling allo-SCT for adults with AML

“…15,17,18 The in vivo administration of alemtuzumab results in profound immunosuppression, significantly reducing GVHD when compared with T-cell replete transplants for a variety of haematological malignancies. 12,13,[18][19][20][21][22][23][24][25] Conversely, as a result of the depletion of the lymphocytes and APCs involved in GVL as well as GVHD, alemtuzumab has been associated with increased risk of relapse 26 In addition, alemtuzumab is associated with poor immune recovery post transplant, 26 and it is now apparent that an increased risk of infections after transplant with alemtuzumab is a significant cause of morbidity and mortality. 27,28 Balancing these competing effects in favour of low non-relapse mortality is the goal of the effective use of alemtuzumab.…”